drug-induced pancreatitis christi riley

Drug-Induced Drug-Induced PancreatitisPancreatitis

Christi RileyChristi RileyPharm.D. Candidate 2009Pharm.D. Candidate 2009

October 16, 2008October 16, 2008University of Kentucky College of PharmacyUniversity of Kentucky College of Pharmacy

ObjectivesObjectives

Understand the diagnosis and etiology of Understand the diagnosis and etiology of acute pancreatitisacute pancreatitis

Understand the drugs implicated in Understand the drugs implicated in drug-induced pancreatitisdrug-induced pancreatitis

Understand treatments and complications Understand treatments and complications associated with drug-induced pancreatitisassociated with drug-induced pancreatitis

PhysiologyPhysiology

Pancreas is responsible for the Pancreas is responsible for the production of insulin and digestive production of insulin and digestive enzymesenzymes

Major enzymes:Major enzymes:– AmylaseAmylase– LipaseLipase– TrypsinTrypsin

Whitcomb, N Engl J Med. 2006 May 18;354(20):2142-50

PathophysiologyPathophysiology

Acute pancreatitis results from inappropriate Acute pancreatitis results from inappropriate activation of trypsinogen to trypsinactivation of trypsinogen to trypsinFailure to eliminate active trypsinFailure to eliminate active trypsinDigestive enzymes cause pancreatic injury and Digestive enzymes cause pancreatic injury and inflammation inflammation The acute inflammatory response can cause The acute inflammatory response can cause tissue damage, a systemic inflammatory tissue damage, a systemic inflammatory response syndrome, multi-organ failure, or response syndrome, multi-organ failure, or deathdeath


Acute PancreatitisAcute Pancreatitis

IncidenceIncidence– 220,000 patients in 2007220,000 patients in 2007Mortality - 10-30%Mortality - 10-30%African Americans > CaucasiansAfrican Americans > CaucasiansMales > Females Males > Females – Males = AlcoholMales = Alcohol– Females = Biliary tract disease Females = Biliary tract disease Age varies from 30-70 yearsAge varies from 30-70 years


Risk FactorsRisk Factors

Biliary tract disease (40%)Biliary tract disease (40%)Alcohol (35%) Alcohol (35%) Post-ERCP (4%)Post-ERCP (4%)Drugs (2%) Drugs (2%) Trauma (1.5%) Trauma (1.5%) Idiopathic (10%)Idiopathic (10%)

Gardner, TB, Acute Pancreatitis, Jun 10, 2008, http://www.emedicine.com

““I Get Smashed”I Get Smashed”I - idiopathic I - idiopathic G - gallstones G - gallstones E - ethanol (alcohol)E - ethanol (alcohol) T - trauma T - trauma S - steroids S - steroids M - mumps and other viruses M - mumps and other viruses A - autoimmune disease A - autoimmune disease S - scorpion sting/ snake bite S - scorpion sting/ snake bite H - hypercalcemia, hyperlipidemiaH - hypercalcemia, hyperlipidemiaE - ERCP E - ERCP D - drugsD - drugs


Signs and SymptomsSigns and Symptoms

Abdominal pain – Cardinal SymptomAbdominal pain – Cardinal Symptom– Dull, boring, and steadyDull, boring, and steady– Sudden onset, gradually intensifiesSudden onset, gradually intensifies– Epigastric regionEpigastric region– Lasting more than one dayLasting more than one day

Nausea/Vomiting/DiarrheaNausea/Vomiting/DiarrheaElevated Pancreatic EnzymesElevated Pancreatic EnzymesPhysical examination findings Physical examination findings – Fever Fever – Tachycardia Tachycardia – Muscular guardingMuscular guarding– Abdominal distensionAbdominal distension

Journal of Gastroenterology and Hepatology (2002) 17 (Suppl.) S15–S39

Amylase and LipaseAmylase and Lipase

KEY enzymes in diagnosis of APKEY enzymes in diagnosis of AP

Serum levels begin to rise 2 to 12 Serum levels begin to rise 2 to 12 hours from onsethours from onset

Lipase can remain elevated up to 14 Lipase can remain elevated up to 14 daysdays

Lipase levels 2.5-3x Amylase indicates Lipase levels 2.5-3x Amylase indicates pancreatitis due to alcoholpancreatitis due to alcohol

Lipase levels will remain normal in Lipase levels will remain normal in some non-pancreatic conditionssome non-pancreatic conditions

Drug-Induced PancreatitisDrug-Induced Pancreatitis

Medications account for 2% of APMedications account for 2% of AP

Difficult to make definitive diagnosisDifficult to make definitive diagnosis

DIP is relatively rare when compared to DIP is relatively rare when compared to number of potentially toxic drugsnumber of potentially toxic drugs

Many isolated and sporadic reports of Many isolated and sporadic reports of DIPDIP


DIP Diagnostic Algorithm

J Clin Gastroenterology, September 2005

Medications associated with Medications associated with DIPDIP

Most commonMost common– AzathioprineAzathioprine– Valproic acidValproic acid– MesalamineMesalamine– EstrogensEstrogens– FurosemideFurosemide– HMG-CoA reductase inhibitorsHMG-CoA reductase inhibitors– IsoniazidIsoniazid– MercaptopurineMercaptopurine

Trivedi, Drug-Induced Pancreatitis: An Update, J Clin Gastroenterology, 2005, Sep, 39 (8); 709-716

Medications associated with Medications associated with DIPDIP

Less common drugsLess common drugs– RifampinRifampin– LamivudineLamivudine– HydrochlorothiazideHydrochlorothiazide– CisplatinCisplatin– CarbamazepineCarbamazepine– AcetaminophenAcetaminophen– OctreotideOctreotide

Trivedi, Drug-Induced Pancreatitis: An Update, J Clin Gastroenterology, 2005, Sep, 39 (8); 709-716

Byetta (exenatide)Byetta (exenatide)FDA ALERT on the topic of acute pancreatitis in patients taking FDA ALERT on the topic of acute pancreatitis in patients taking Byetta Byetta

Information for Healthcare Professionals – ExenatideInformation for Healthcare Professionals – Exenatide Update 8/18/2008:Update 8/18/2008: Since October 2007, FDA has received reports Since October 2007, FDA has received reports of 6 cases of hemorrhagic or necrotizing pancreatitis in patients of 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta. Of the 6 cases of hemorrhagic or necrotizing taking Byetta. Of the 6 cases of hemorrhagic or necrotizing pancreatitis, all patients required hospitalization, two patients died pancreatitis, all patients required hospitalization, two patients died and four patients were recovering at time of reporting.and four patients were recovering at time of reporting.FDA ALERT [10/2007]:FDA ALERT [10/2007]: FDA has reviewed 30 postmarketing FDA has reviewed 30 postmarketing reports of acute pancreatitis in patients taking Byetta. An reports of acute pancreatitis in patients taking Byetta. An association between Byetta and acute pancreatitis is suspected in association between Byetta and acute pancreatitis is suspected in some of these cases. Healthcare professionals should instruct some of these cases. Healthcare professionals should instruct patients taking Byetta to seek prompt medical care if they patients taking Byetta to seek prompt medical care if they experience unexplained persistent severe abdominal pain which experience unexplained persistent severe abdominal pain which may or may not be accompanied by vomiting. If pancreatitis is may or may not be accompanied by vomiting. If pancreatitis is suspected, Byetta should be discontinued. If pancreatitis is suspected, Byetta should be discontinued. If pancreatitis is confirmed, Byetta should not be restarted unless an alternative confirmed, Byetta should not be restarted unless an alternative etiology is identified.etiology is identified.

FDA, http://www.fda.gov/CDER/Drug/InfoSheets/

Complications of PancreatitisComplications of Pancreatitis

Acute fluid collections Acute fluid collections

Pseudocyst Pseudocyst

Intra-abdominal infections Intra-abdominal infections – Intestinal flora are the predominant source Intestinal flora are the predominant source

of bacteriaof bacteria

Pancreatic necrosis Pancreatic necrosis

DeathDeath


Treatments Treatments

Pain ControlPain Control– IV pain medications, avoid exacerbationsIV pain medications, avoid exacerbations

Bowel Rest and IV HydrationBowel Rest and IV Hydration

Supportive CareSupportive Care– Blood glucose monitoring Blood glucose monitoring

Nutritional SupportNutritional Support– Enteral feedings or TPNEnteral feedings or TPN

ERCP ERCP

AntibioticsAntibiotics

SurgerySurgeryJournal of Gastroenterology and Hepatology (2002) 17 (Suppl.) S15–S39


Use of Abx is controversialUse of Abx is controversial

Prophylactic Abx is not recommendedProphylactic Abx is not recommended

Reserved for Necrotizing PancreatitisReserved for Necrotizing Pancreatitis

Abx are appropriate for fever, Abx are appropriate for fever, leukocytosis, and organ failure with leukocytosis, and organ failure with confirmed positive culturesconfirmed positive cultures



Coverage of Gram – and Gram + Coverage of Gram – and Gram + bacteriabacteriaFluoroquinolonesFluoroquinolonesImipenem-cilastatin Imipenem-cilastatin MetronidazoleMetronidazoleCiprofloxacinCiprofloxacinZosyn or UnasynZosyn or Unasyn– Intrabdominal infectionsIntrabdominal infections

Gastroenterologist. 1997 Jun;5(2):157-64

Pharmacist RolePharmacist Role

Be aware of potential for DIPBe aware of potential for DIPRule out medications as causeRule out medications as causeSuggest appropriate therapiesSuggest appropriate therapiesGlucose monitoring/interventionsGlucose monitoring/interventionsReporting of Adverse Drug events to track Reporting of Adverse Drug events to track incidence and severity of DIPincidence and severity of DIPFDA Center for Drug Evaluation and FDA Center for Drug Evaluation and Research Research http://www.fda.gov/cder/index.html http://www.fda.gov/cder/index.html

SummarySummary

Acute pancreatitis can be a medical Acute pancreatitis can be a medical emergencyemergency

Proper medical attention and treatment is Proper medical attention and treatment is necessarynecessary

Many times, cause is unknown, therefore Many times, cause is unknown, therefore we must rule out all possible etiologies we must rule out all possible etiologies including medicationsincluding medications

Drug-Induced Drug-Induced PancreatitisPancreatitis

Christi RileyChristi RileyPharm.D. Candidate 2009Pharm.D. Candidate 2009

October 16, 2008October 16, 2008University of Kentucky College of PharmacyUniversity of Kentucky College of Pharmacy

drug-induced pancreatitis christi riley

Documents

topic of acute pancreatitis

n engl j

acute pancreatitisincidence220

acute inflammatory response

pancreatic injury

lipasekey enzymes

diagnosis of apserum

alcohollipase levels